This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In preliminary experiments we have determined that transgenic over-expression of Ep-CAM outside the endocrine compartment results in large islets. The goal of this project is to test whether transgenic over-expression of Ep-CAM in murine adult pancreatic progenitors, identified by the expression of Sox9, leads to the expansion of this cellular pool and fosters the development of new beta-cells. Using a bigenic transgenic system, our plan is to activate Ep-CAM over-expression specifically in the Sox9+ adult ductal cell compartment. In a second series of experiments we will also use a tetracysteine-tagged Ep-CAM construct (hEp-CAM-TC) to generate transgenic mice. The rationale for generating this line transgenics is to be able to perform correlative optical/electron microscopy morphometric studies of cell-cell junctions, both in vitro and in vivo, following correlative microscopic technologies recently developed at the NCMIR (UCSD).